Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twelve patients suffering from rheumatoid arthritis and having swollen knees were treated with 1.1 g/day of sodium naproxen administered in one dose, daily for 5 days. The 72-h wash-out period was verified by the absence of any nonsteroidal anti-inflammatory drug using a HPLC screening. Blood and synovial fluid samples were drawn just before treatment and 24 h after the last dose. Eicosanoids (PGE2, 6-keto-PGF1 alpha, TXB2, LTB4, LTC4) in synovial fluid were determined by immunoenzymatic assays. In plasma and synovial fluid, hyaluronic acid was assayed by radiometric assay and sodium naproxen by HPLC. Free drug was determined by equilibrium dialysis. Statistical analysis used nonparametric tests. Pain relief (evaluated on a visual scale), morning stiffness, and scores on the Lee and Ritchie indices all decreased significantly, as did PGE2 and LTB4 concentrations. The decrease in 6-keto-PGF1 alpha and TXB2 was not significant. No significant change was found for LTC4 and hyaluronic acid. Total concentrations of sodium naproxen were equivalent in plasma (16.1 micrograms.ml-1) and synovial fluid (18.9 micrograms.ml-1). Free fractions were significantly higher in synovial fluid (0.14%) than in plasma (0.11%), as shown by binding of the drug to human serum albumin, at various protein concentrations. Interestingly, the clinical efficacy, as shown by decreases in morning stiffness and in the Lee index score, correlated with the free concentration of naproxen in synovial fluid.
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PMID:Sodium naproxen: concentration and effect on inflammatory response mediators in human rheumatoid synovial fluid. 800 84

Methotrexate (MTX) has become an important drug in the treatment of rheumatoid arthritis (RA). The American College of Rheumatology convened a committee to assess the risks of development of clinically significant liver disease (CSLD) during MTX treatment, to evaluate the risk and role of surveillance liver biopsies, and to provide recommendations about monitoring patients for liver toxicity. The committee recommends obtaining liver blood tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase, albumin, bilirubin), hepatitis B and C serologic studies, and other standard tests including complete blood cell count and serum creatinine tests prior to starting treatment with MTX. A pretreatment liver biopsy should be considered only for patients with a history of prior excessive alcohol consumption, persistently abnormal baseline AST values, or chronic hepatitis B or C infection. At intervals of every 4-8 weeks the AST, ALT, and albumin levels should be monitored. Routine surveillance liver biopsies are not recommended for RA patients receiving traditional doses of MTX. However, a biopsy should be performed if a patient develops persistent abnormalities on liver blood tests. These are defined as elevations (above the upper limit of laboratory normal) in the AST in 5 of 9 determinations within a given 12-month interval (6 of 12 if tests are performed monthly) or a decrease in serum albumin below the normal range. The recommendations for monitoring and selection of patients for liver biopsy identify patients at potential risk for CSLD, and thus significantly reduce the number or patients who would be exposed to this procedure. Close monitoring is essential to reduce the risk of unrecognized serious liver disease. These recommendations should be revised as necessary to reflect new and compelling information.
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PMID:Methotrexate for rheumatoid arthritis. Suggested guidelines for monitoring liver toxicity. American College of Rheumatology. 798 33

We have reported that fibronectin fragments (Fn-f) cause cartilage damage in vitro by causing enhanced release of proteases. In order to determine whether the Fn-f can damage cartilage in vivo, we have injected native fibronectin (Fn) and Fn-f into adolescent rabbit knee joints. After 7 days, tissue was analyzed by histochemical and biochemical techniques and remaining proteoglycans quantified. Injection of 0.6 or 3 microM Fn-f caused up to a 70% loss in total cartilage proteoglycan while native Fn, rabbit serum albumin or an Arg-Gly-Asp-Ser synthetic peptide, derived from the cell-binding domain of Fn, did not cause damage. Our results suggest that this Fn-f/damage model may be useful for generating cartilage damage in vivo for other studies. Since Fn-f have been detected in synovial fluids from joints of patients with rheumatoid arthritis and osteoarthritis, our results are consistent with the notion that Fn-F mediated damage may occur in vivo.
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PMID:Intraarticular injection of fibronectin fragments causes severe depletion of cartilage proteoglycans in vivo. 823 23

The present study was undertaken to identify the cartilage matrix molecules that are bound with intermolecular disulfide bonds to IgG and serum albumin molecules recovered from the articular cartilage of patients with rheumatoid arthritis (RA) or osteoarthritis (OA). The cartilage specimens were extracted sequentially with three changes of neutral buffer, three changes of 6 M guanidine hydrochloride and then partially degraded with bacterial collagenase. The extracted IgG and albumin, along with matrix molecules bound to these proteins, were isolated with affinity chromatography using antibodies to IgG or human serum albumin conjugated to agarose beads. The isolated materials were characterized with sodium dodecyl sulfate polyacrylamide gel electrophoresis and transfer blotting, using specific antibodies to IgG, albumin, and proteoglycans. In the isolated materials, heteropolymers with IgG or albumin were identified. These polymers contained keratan sulfate and less frequently chondroitin-4-sulfate and chondroitin-6-sulfate. These findings identified the keratan sulfate rich proteoglycans, prevalent at the surface of joint cartilage, as the most common cartilage matrix molecules that are covalently bound to IgG or to serum albumin by disulfide bonds in the articular cartilage of patients with RA or OA.
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PMID:Immunoglobulin G and serum albumin isolated from the articular cartilage of patients with rheumatoid arthritis or osteoarthritis contain covalent heteropolymers with proteoglycans. 823 91

Rapamycin (RAPA), a potent immunosuppressive agent that prevents organ graft rejection in animal models of transplantation, possesses a mechanism of action different than that of cyclosporin A and FK-506. In this study, the pharmacological activity of RAPA in a variety of immune and inflammatory models was assessed in order to define better its potential utility as an antiarthritic agent. RAPA inhibited T cell-mediated inflammation in mouse methylated bovine serum albumin-induced delayed-type hypersensitivity (ED40 = 4.7 mg/kg p.o.) and produced oral ED50 of 2.0 mg/kg against developing adjuvant arthritis in rats (3-day dosing schedule) and 9.5 mg/kg in established adjuvant arthritis in rats (daily dosing schedule). In both models of adjuvant arthritis, effects of RAPA were maintained even after cessation of drug dosing. In contrast, after discontinuation of cyclosporin A (5- and 10-mg/kg doses), disease activity returned. RAPA was also effective in another T cell-mediated model, experimental allergic encephalomyelitis (ED50 approximately 5 mg/kg p.o.). At higher doses, RAPA significantly inhibited carrageenan paw edema in rats, a model of acute inflammation (ED40, 56 mg/kg p.o.), without increasing serum corticosterone levels. In this model, doses approximately 10 to 20 times greater than active doses in T cell-mediated models were required. RAPA at 1 to 50 microM did not inhibit in vitro human synovial phospholipase A2 or 5-lipoxygenase and cyclo-oxygenase activity in the human blood leukocyte assay. The total profile of RAPA suggests that it may be effective in the treatment of rheumatoid arthritis, multiple sclerosis and other autoimmune diseases.
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PMID:Rapamycin, a potential disease-modifying antiarthritic drug. 835 84

Interleukin 6 (IL-6) is a multifunctional cytokine and plays an important role in host defense mechanisms. Enhanced production of IL-6 has been reported in polyclonal B-cell abnormalities and autoimmune diseases such as rheumatoid arthritis (RA). To investigate the role of IL-6 inflammatory joint diseases, serum IL-6 levels of three animal models of RA, namely type II collagen (CII)-induced murine, rat arthritis and adjuvant-induced rat arthritis, were monitored. In these models, serum IL-6 increased with the development of arthritis. Serum IL-6 was not elevated by immunization with a non-arthritogenic immunogen such as bovine type I collagen (CI) and bovine serum albumin (BSA) to DBA/1J mice. The serum IL-6 level was correlated well with the severity of adjuvant-induced arthritis. The elevated IL-6 in sera may be associated with the overproduction of IL-6 at the arthritis paws, because higher IL-6 activity was detected in the homogenates of arthritic paws as compared with the control paws. Synovial fibroblasts were isolated from the arthritis knee joints of DBA/1J mice. These cells expressed type I interleukin 1 (IL-1) receptor constitutively and produced large amounts of IL-6 in response to IL-1 in vitro. Enhanced production of IL-1 was also detected at the arthritis paws. These results suggest that the elevated IL-6 in sera may be associated with the overproduced IL-6 in response to the increased IL-1 at the arthritic joints. Serum IL-6 may be a useful parameter for monitoring disease activity.
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PMID:Enhanced expression of interleukin 6 in rat and murine arthritis models. 836 23

Nutritional status was studied over a period of 13 months in 34 patients with rheumatoid arthritis (RA). Seventeen patients fasted for 7-10 days, were then transferred to a gluten-free vegan diet for 3.5 months and finally to a lactovegetarian diet for 9 months. The remaining 17 patients followed a "normal" diet. After one month, the values for body mass index (BMI) and triceps skinfold thickness (TSF) were significantly reduced in the diet group compared with the values at inclusion (p < 0.001), whereas upper arm muscle area (UAMA) was not significantly reduced. Evaluation of the whole study course revealed a significantly lower BMI (p = 0.04) and TSF (p < 0.01) in the diet group compared with the control group. The concentration of insulin-like growth factor 1 (IGF1) was significantly reduced in the diet group after one month compared with the value at inclusion (p = 0.01), but the overall difference between the two groups was not significant. There were no overall significant differences with regard to VAMA, concentration of serum albumin, haemoglobin, ferritin, zinc and copper between the two groups. Thus fast, followed by diet manipulations for one year, had a minor impact on nutritional status in patients with RA.
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PMID:The influence of fast and vegetarian diet on parameters of nutritional status in patients with rheumatoid arthritis. 846 14

Human immunoglobulins treated at 55 degrees C in vitro are able to interact with maleylated bovine serum albumin (mBSA), but not with unmodified BSA. Gel filtration experiments demonstrated that the mBSA binding is associated with a high molecular weight complex of aggregated IgG. This aggregated IgG with binding capacity for mBSA could also be generated in vitro by treatment of human IgG at 37 degrees C or 40 degrees C and by incubation with human neutrophils. Furthermore, IgG aggregates with binding activity for mBSA could be detected in untreated synovial fluids from rheumatoid arthritis patients, indicating that these complexes occur in vivo. The phenomenon of binding to aggregated IgG was extended to other modified proteins such as maleylated human serum albumin (mHSA), acetyl low density lipoprotein (Ac-LDL) and BSA reacted with oxidized linolenic acid. Soluble forms of these modified proteins were able to compete for the interaction between aggregated IgG and surface-bound mBSA. We also found that aggregated IgG enhanced the Ac-LDL-dependent foam cell formation. These findings suggest a role for aggregated IgG in the metabolism of oxidized proteins.
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PMID:Aggregated human immunoglobulins bind to modified proteins. 848 5

Diseases caused by occupational exposure to sensitizing metals including platinum (Pt), rhodium (Rh), nickel (Ni), chromium (Cr), cobalt (Co), gold (Au), mercury (Hg), zirconium (Zr) and beryllium (Be) are reviewed. Allergic reactions induced by the metals are described according to the classification by Coombs and Gell. Metals with unproven sensitizing potential are not discussed if reports on these are either very rare or devoid of convincing evidence for allergic involvement. The sensitizing metals are haptens which are not themselves able to act as antigens. There is evidence that combination of the metals with circulating or tissue protein gives rise to new antigens. An alternative hypothesis is that these metals interfere with the antigen recognition step of the immune response. Immunomodulatory effects or immunotoxicity of the metals may be also involved in metal-induced hypersensitivity. Occupational exposure to Pt, Rh, Ni, Cr, and Co causes allergic asthma via type I allergic reaction in which serum from affected individuals shows specific IgE antibodies against mental-human serum albumin conjugates. Some rheumatoid arthritis patients treated with gold salt therapy develop glomerulonephritis, thrombocytopenia, or agranulocytosis, which arise from type II and/or type III allergic reactions. Occupational exposure to mercury causes glomerulonephritis in which involvement of type III reaction is suggested. Type IV hypersensitivity reaction of the skin also takes place following exposure to the metals: allergic contact dermatitis is evoked by exposure to Ni, Cr, Co, Rh, and Hg; cutaneous granuloma is formed by contact with Zr and Be. Be is also a sensitizer of the lungs, resulting in granulomatous disease. Diagnosis of metal-induced allergic diseases is made on the basis of allergological tests with metal antigens including skin tests, radioallergosorbent test for specific antibody, lymphocyte transformation test, macrophage migration inhibition test, and provocation test. Atopy is a predisposing factor and smoking is a risk factor for developing metal-induced asthma. Evidence for genetic factors in the development of metal contact dermatitis is conflicting, although animal models implicate genetic factors in skin sensitization with some metals and respiratory sensitization with Be. Skin irritation, forearm injury, complication with atopic dermatitis and concomitant sensitization to other agents are determinants for prognosis of the dermatitis. Epidemiological reports of occupational diseases from allergic reactions to metals in industries are reviewed with respect to prevalence and allergic manifestations. There is a report on a clinical trial of hyposensitization with Pt in a platinum asthma patient. Predictive methods for evaluating sensitization potential of metals have been developed and new methods, which quantify potential more objectively, are sought.
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PMID:[Occupational diseases caused by exposure to sensitizing metals]. 851 Mar 47

Severe adverse effects of low-dose methotrexate (less than 20 mg per week) are believed to be rare. We report eight cases of severe tricytopenia or pancytopenia seen in two medical departments of the same hospital in patients receiving low-dose methotrexate. Three patients had been under methotrexate for less than one month. Of the six patients with joint disease, five had rheumatoid arthritis and one psoriatic arthritis. A review of the literature found 92 previously reported cases of severe tricytopenia or pancytopenia induced by low-dose methotrexate. Of the total of 100 cases, 24 were fatal and 25 occurred within one month of treatment initiation. Potential risk factors were identifiable retrospectively in at least 50% of cases but were not all predictable or present at treatment initiation. In 30% of cases, no explanation for the hematologic complication was found, and in an additional 20% missing data precluded definite conclusions. The role of the risk factors incriminated in the literature is discussed. Although infrequent, cytopenia is a severe complication of methotrexate therapy that warrants a number of precautions, including periodic creatinine clearance and serum albumin determinations. Furthermore, the weekly dosing schedule should be printed on methotrexate boxes.
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PMID:Pancytopenia and severe cytopenia induced by low-dose methotrexate. Eight case-reports and a review of one hundred cases from the literature (with twenty-four deaths) 905 66


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